Investigating hesperetin nanocrystals with tailor-made sizes for the prevention and treatment of Alzheimer’s disease

Stahr, Pascal-L.; Grewal, Rekha; Eckert, Gunter P.; Keck, Cornelia M.

doi:10.1007/s13346-020-00888-0

Cited by 24 publications

(18 citation statements)

References 31 publications

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“…A possible explanation could be the particle size of the nanocrystals. In a previous study, we determined that Hst with smaller particles had a greater effect on elevating ATP levels in SH-SY5Y-APP wt cells compared to larger ones [25]. Similar, most studies have shown that the particle size has an impact on cell functions [48][49][50].…”

Section: Effect Of Hesperetin On Mitochondrial Function In Sh-sy5y-mock and -App 695 Cellsmentioning

confidence: 53%

“…All vials were stirred on a magnetic stirring plate (IKA RCT standard, Haan, Germany) at 1200 rpm in ice water for 8 h. After production and before treatment of cells, particle size was strictly monitored. The average particle size was determined by photon correlation spectroscopy using a ZetaSizer NanoZS (Malvern-Panalytical, Kassel, Germany), laser diffraction using a Mastersizer 3000 (Malvern-Panalytical, Kassel, Germany), and light microscopy using an Olympus BX53 light microscope (Olympus Cooperation, Tokyo, Japan) equipped with an Olympus SC50 CMOS color camera (Olympus Soft Imaging Solutions GmbH, Nord, Germany) according to [25]. Since polyphenols have the potential to act as pan-assay interference compounds [36], we used PAINS-Remover at https://www.…”

Section: Hesperetin Nanocrystalsmentioning

confidence: 99%

“…We recently reported high antioxidative capacity of Hst nanocrystals using a DPPH assay [25]. In a study using PC12 cells, HstP provided protection against H 2 O 2 -induced oxidative stress.…”

Section: Introductionmentioning

confidence: 98%

“…Hst is a natural flavonoid with high antioxidant activity, poor water solubility, and lipophilic characteristics [25]. Even though liposomes are rather crude biomimetic models of biological cell membranes, data have shown that liposome electrokinetic chromatography (LEKC) can be used to predict the behavior of compounds in living systems [26].…”

Section: Introductionmentioning

confidence: 99%

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Hesperetin Nanocrystals Improve Mitochondrial Function in a Cell Model of Early Alzheimer Disease

et al. 2021

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Mitochondrial dysfunction represents a hallmark of both brain aging and age-related neurodegenerative disorders including Alzheimer disease (AD). AD-related mitochondrial dysfunction is characterized by an impaired electron transport chain (ETC), subsequent decreased adenosine triphoshpate (ATP) levels, and elevated generation of reactive oxygen species (ROS). The bioactive citrus flavanone hesperetin (Hst) is known to modulate inflammatory response, to function as an antioxidant, and to provide neuroprotective properties. The efficacy in improving mitochondrial dysfunction of Hst nanocrystals (HstN) with increased bioavailability has not yet been investigated. Human SH-SY5Y cells harboring neuronal amyloid precursor protein (APP695) acted as a model for the initial phase of AD. MOCK-transfected cells served as controls. The energetic metabolite ATP was determined using a luciferase-catalyzed bioluminescence assay. The activity of mitochondrial respiration chain complexes was assessed by high-resolution respirometry using a Clarke electrode. Expression levels of mitochondrial respiratory chain complex genes were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The levels of amyloid β-protein (Aβ1-40) were measured using homogeneous time-resolved fluorescence (HTRF). ROS levels, peroxidase activity, and cytochrome c activity were determined using a fluorescence assay. Compared to pure Hst dissolved in ethanol (HstP), SH-SY5Y-APP695 cells incubated with HstN resulted in significantly reduced mitochondrial dysfunction: ATP levels and respiratory chain complex activity significantly increased. Gene expression levels of RCC I, IV, and V were significantly upregulated. In comparison, the effects of HstN on SY5Y-MOCK control cells were relatively small. Pure Hst dissolved in ethanol (HstP) had almost no effect on both cell lines. Neither HstN nor HstP led to significant changes in Aβ1-40 levels. HstN and HstP were both shown to lower peroxidase activity significantly. Furthermore, HstN significantly reduced cytochrome c activity, whereas HstP had a significant effect on reducing ROS in SH-SY5Y-APP695 cells. Thus, it seems that the mechanisms involved may not be linked to altered Aβ production. Nanoflavonoids such as HstN have the potential to prevent mitochondria against dysfunction. Compared to its pure form, HstN showed a greater effect in combatting mitochondrial dysfunction. Further studies should evaluate whether HstN protects against age-related mitochondrial dysfunction and thus may contribute to late-onset AD.

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Section: Effect Of Hesperetin On Mitochondrial Function In Sh-sy5y-mock and -App 695 Cellsmentioning

confidence: 53%

Section: Hesperetin Nanocrystalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Hesperetin Nanocrystals Improve Mitochondrial Function in a Cell Model of Early Alzheimer Disease

et al. 2021

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“…A similar double-targeted nanosystem loaded with RESV showed neuroprotective effects in an AD mouse model [232]. [236,237] NLCs: nanostructured lipid carriers, SLN: solid lipid nanoparticles, SPION: superparamagnetic iron oxide nanoparticles, SLN/RVG29/TPP: Solid lipid nanoparticles attached to rabies virus glycoprotein (RVG29) and triphenylphosphonium (TPP) moiety, GSH: glutathione, GSH-PX: glutathione peroxidase, SOD: superoxide dismutase, CAT: catalase, ETC: electron transport chain, Aβ: amyloid β protein, RES: reticuloendothelial system, PD: Parkinson disease, AD: Alzheimer's disease.…”

Section: Nanosystems Containing Antioxidative and Neuroprotective Plant Chemicals To Repair Mitochondrial Function In Neurodegenerationmentioning

confidence: 99%

Nanotechnology-Based Drug Delivery Strategies to Repair the Mitochondrial Function in Neuroinflammatory and Neurodegenerative Diseases

2021

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Mitochondria are vital organelles in eukaryotic cells that control diverse physiological processes related to energy production, calcium homeostasis, the generation of reactive oxygen species, and cell death. Several studies have demonstrated that structural and functional mitochondrial disturbances are involved in the development of different neuroinflammatory (NI) and neurodegenerative (ND) diseases (NI&NDDs) such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Remarkably, counteracting mitochondrial impairment by genetic or pharmacologic treatment ameliorates neurodegeneration and clinical disability in animal models of these diseases. Therefore, the development of nanosystems enabling the sustained and selective delivery of mitochondria-targeted drugs is a novel and effective strategy to tackle NI&NDDs. In this review, we outline the impact of mitochondrial dysfunction associated with unbalanced mitochondrial dynamics, altered mitophagy, oxidative stress, energy deficit, and proteinopathies in NI&NDDs. In addition, we review different strategies for selective mitochondria-specific ligand targeting and discuss novel nanomaterials, nanozymes, and drug-loaded nanosystems developed to repair mitochondrial function and their therapeutic benefits protecting against oxidative stress, restoring cell energy production, preventing cell death, inhibiting protein aggregates, and improving motor and cognitive disability in cellular and animal models of different NI&NDDs.

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Recent Advances in Nanocrystals Heralding Greater Potential in Brain Delivery

Mule

Khairnar

Shukla

2022

Part & Part Syst Charact

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conducted in order to develop preventive and therapeutic treatment modalities for brain-related disorders, the complications in brain delivery exist mostly due to the presence of the blood-brain barrier (BBB). Nanotechnology offers a promising platform for brain drug delivery for the management of various disorders. Nanotechnology tools in pharmaceutical applications have the potential to revolutionize the whole research and development venture concerning to drug delivery. Various nanotechnology-based strategies including polymeric nanoparticles, nanocrystals (NCs), liposomes, dendrimers, and quantum dots are the recent area of thorough research in brain drug delivery. Therapeutic, as well as diagnostic potentials of these nanosystems, are being explored for brain-related disorders.Drug NCs are particles fabricated using the pure solid drug with content up to 100%; they are often stabilized by polymeric steric stabilizers or surfactants. In early 1990, NCs were designed, and after the year 2000, the first product of NCs was marketed. Targeted drug delivery to the desired site can further be achieved with the surface functionalization of NCs. The high surface-to-volume ratio of NCs is the reason for the greater interaction of NCs with the cells/ tissue surface which ultimately improves the bioavailability of the drug. Relatively convenient methods of preparation and easy scale-up of NCs are other factors that highlight NCs as the most suitable nanosystems for the delivery of drugs.This review is particularly focused on the NCs-based drug delivery approaches to the brain for the management of a variety of brain-related disorders. Along with NCs, other nanosystems are briefly described. The recent developments in the area specified hereby along with the various challenges associated with brain delivery of drugs and the improvements that can be observed with the application of NCs in brain delivery along with the strategic designing of NCs so as to overcome the barriers in brain delivery of NCs are extensively discussed in this review. Blood-Brain Barrier: A Major ChallengeThe BBB is a key challenge for NCs because it largely hinders the targeted brain delivery of therapeutic moieties. The number of drug delivery systems fail to deliver drug molecules due to About 90% of natural/synthetic origin new drugs under the discovery process are facing problems related to poor aqueous solubility. Nanotechnologymediated approaches are proven to be effective in the development of such drug molecules. Nanocrystals (NCs) are the pure solid crystalline particulates with a mean diameter smaller than 1 µm and are primarily comprised of only the drug along with the stabilizers. NCs technology has proven to be a potential strategy to enhance the solubility and the therapeutic efficacy of BCS class IV and class II drugs. Such potential of NCs offers new prospects for advancement in targeted brain delivery in various disorders. The main hurdle for the delivery of the drug is blood brain barrier (BBB) which protects central nervous syste...

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Investigating hesperetin nanocrystals with tailor-made sizes for the prevention and treatment of Alzheimer’s disease

Cited by 24 publications

References 31 publications

Hesperetin Nanocrystals Improve Mitochondrial Function in a Cell Model of Early Alzheimer Disease

Hesperetin Nanocrystals Improve Mitochondrial Function in a Cell Model of Early Alzheimer Disease

Nanotechnology-Based Drug Delivery Strategies to Repair the Mitochondrial Function in Neuroinflammatory and Neurodegenerative Diseases

Recent Advances in Nanocrystals Heralding Greater Potential in Brain Delivery

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